Precision Medicine in Non Communicable Diseases.

Non-communicable diseases (NCDs) are the leading cause of death and disease burden globally, cardiovascular diseases (CVDs) account for the major part of death related to NCDs followed by different types of cancer, chronic obstructive pulmonary disease (COPD), and diabetes. As the World Health Organization (WHO) and the United Nations have announced a 25% reduction in mortality of NCDs by 2025, different communities need to adopt preventive strategies for achieving this goal. Personalized medicine approach as a predictive and preventive strategy aims for a better therapeutic goal to the patients to maximize benefits and reduce harms. The clinical benefits of this approach are already realized in cancer targeted therapy, and its impact on other conditions needs more studies in different societies. In this review, we essentially describe the concept of personalized (or precision) medicine in association with NCDs and the future of precision medicine in prediction, prevention, and personalized treatment.

on-communicable diseases (NCDs)mainly cancers, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVDs), and chronic respiratory diseases (CRDs) are the biggest cause of death worldwide (1). More than 36 million people die annually from NCDs which account for 63% of all deaths globally (1,2). The World Health Organization (WHO) developed an NCD global action plan and determined nine targets that have to be achieved to reach a 25% relative reduction in premature mortality from the four major NCDs (i.e., CVDs, cancers, CRDs, and diabetes) by Medicine has always tried to be as precise as possible. The terms "personalized", "precision", "stratified", "individualized" and "P4 medicine" have been used interchangeably by many clinicians and researchers (4). Precision medicine which was defined synonymously personalized medicine or individualized medicine is really not a new invention (5). In the context of precision medicine, a new taxonomy describes the common diseases based on their molecular profile in addition to traditional signs and symptoms (6). Precision medicine is an emerging approach for prediction, early prevention and treatment that takes into account individual variability in genes for each person. Precision medicine is quickly considered as the art of medicine for creating personalized assessments of health and diseases that are derived from omics (i.e., genomic, transcriptomic, proteomic, metabolomic) profile (7,8). Precision medicine is much more well-known in cancer than in diabetes, where omics sciences help to perform the targeted therapy.
The genetic architectures of cancer and diabetes are completely different as in genetic triggers both type 1 (T1D) and type 2 diabetes (T2D) are caused by germline variants with modest effect, whereas specific somatic mutation in a particular cancer cell type initiates cancer development (7).

Precision type 2 diabetes medicine
Diabetes is a significant public health problem worldwide that is recognized as a considerable threat to human health (9). Hence, there is an urgent need to apply novel intervention which predicts and prevents diabetes. Evidence suggests that early treatment is crucial for the prevention of diabetes complications. Current treatment guidelines are restricted because of poor metabolic control of progressed diabetes. Although diabetes is related to insulin deficiency and elevated blood glucose, it is really a mixture of diseases and is much more heterogeneous than the present classification into type 1 and type 2.
A well-defined diabetes classification, particularly for T2D could provide a robust tool to facilitate the implementation of precision medicine for a better diagnosis to a more ideal treatment approaches (10).
In a data-driven cluster analysis in 2018, five replicable clusters of patients with diabetes, with differing disease progression and risk of diabetic complications have been identified. This new substratification might finally help to tailor early treatments to patients who would benefit most, representing the first step towards precision medicine in diabetes management (11).
The American Diabetes Association (ADA) emphasizes the importance of the patient-centered approach, and moves guidelines away from a stepby-step protocol-driven.
Patient-centered care has referred to care that is respectful of and responsive to individual patient preferences, needs, and values. Therefore, patient values guide all clinical decisions, whether based on evidence or expert opinion (12).
In the near future T2D will have been classified into a series of distinct diagnostic types (we could call them type 2A, type 2B) (13). The science and art of medicine come together in precision medicine approach when the clinician is faced with making treatment recommendations for a patient who may not meet the eligibility criteria used in the guidelines as we rely on it in evidencebased medicine approach. Accordingly, we need to look at medical practice in precision-based medicine approach manner which is an innovative approach to tailoring disease prevention and treatment that takes into account genetic make-up, environments, and lifestyles (14). Recognizing that one size does not fit all, the ADA standards provide guidance for when and how to adapt recommendations for an individual (12 Increase of glucose stimulated insulin secretion, functional pancreatic β-cell mass and decrease ofglucagon secretion from pancreatic α-cells

GLP-1 R, CNR1
Insulin Increasingglucose disposal and decreasing hepatic glucose production

Bile acid seqestrants
Glucose lowering (is not known) Decrease in hepatic glucose production (HGP) No gene with relevant effects on treatment response was described

Dopamine-2 agonists
Increasing insulin sensitivity and modulatinghypothalamic regulation of metabolism 

Bromocriptine
No gene with relevant effects on treatment response was described

Amylin mimetrics
Slows gastric emptying, promotingsatiety and reducingthe postprandial glucagons increase The other face of CVD personalized medicine is CVD stratification (e.g., CAD, heart failure, CHD, etc.) which is the identification of a group of patients who will benefit from a specific intervention in tailored treatment (37). Several fundamental classes of CVD medications including β-adrenergic receptor blockers, lipid-lowering drugs, antithrombotic agents and angiotensinconverting enzyme inhibitors have been introduced in CVD pharmacogenomics (38).
CVD precision medicine has the potential to change conventional standards of care, although acceptance of precision medicine will require some evidence for its effectiveness as an approach to care. Clinicians need to know that the data from the omics approach will lead to an actionable step that transforms the routine treatment options.  Zaretsky's study on pembrolizumab -resistant patient models presented that inactivating mutations in JAK1, JAK2, and B2Mcan converse drug resistance in NSCLC patients (67).

Precision colorectal cancer medicine
Colorectal cancer (CRC) is the colon or the rectum cancer that is also called "colon cancer" or "rectal cancer" as well. CRC is the third most frequent cancer in men and the second most common one in women (68

Precision liver cancer medicine
Liver cancer (hepatic cancer) is a cancer that starts from the liver cells or has spread from elsewhere to the liver, known as liver metastasis (93). reported that patients with down-regulated Ecadherin were associated with poor relapse outcomes following radiation therapy (126).

Precision thyroid cancer medicine
Thyroid is a butterfly-shaped gland in the neck, just above the collarbone that makes hormones that support the body work normally.
There Precision medicine changes standard practice and draws from clinical testing, big data sets, and systems biology in order to create an individualspecific phenotype which consequently recognize the best intervention with minimal risk. But an urgent question is whether we are ready for precision medicine in NCDs.